%0 Journal Article %A Xiao, Sa %A Chen, Chao %A Li, Hongyan %A Lin, Kuaile %A Zhou, Weicheng %D 2015 %T A Novel and Practical Synthesis of Ramelteon %U https://acs.figshare.com/articles/journal_contribution/A_Novel_and_Practical_Synthesis_of_Ramelteon/2194390 %R 10.1021/op500386g.s001 %2 https://ndownloader.figshare.com/files/3828718 %K ethylamine compound 13 %K Practical Synthesis %K olefin reduction %K acid %K hydrogenation %K synthesis %K resolution agent %K target compound 1 %K cyano reduction %K nucleophilic reagent %X An efficient and practical process for the synthesis of ramelteon 1, a sedative-hypnotic, is described. Highlights in this synthesis are the usage of acetonitrile as nucleophilic reagent to add to 4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno­[5,4-b]­furan-8-one 2 and the subsequent hydrogenation which successfully implement four processes (debromination, dehydration, olefin reduction, and cyano reduction) into one step to produce the ethylamine compound 13 where dibenzoyl-l-tartaric acid is selected both as an acid to form the salt in the end of hydrogenation and as the resolution agent. Then, target compound 1 is easily obtained from 13 via propionylation. The overall yield in this novel and concise process is almost twice as much as those in the known routes, calculated on compound 2. %I ACS Publications